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Ukukhiqiza okungeziwe kushintsha indlela abacwaningi kanye nezimboni abaklama futhi bakhiqize ngayo amadivayisi amakhemikhali ukuze bahlangabezane nezidingo zabo ezithile. Kulo msebenzi, sibika isibonelo sokuqala se-flow reactor esakhiwe yindlela ye-solid-state metal sheet lamination technique Ultrasonic Additive Manufacturing (UAM) enezingxenye ze-catalytic ezihlanganisiwe ngqo kanye nezinto zokuzwa. Ubuchwepheshe be-UAM abugcini nje ngokunqoba imikhawulo eminingi ehlotshaniswa nokukhiqizwa okungeziwe kwama-chemical reactor, kodwa futhi kwandisa kakhulu amakhono amadivayisi anjalo. Uchungechunge lwezakhi ze-1,2,3-triazole ezibalulekile ngokwebhayoloji ezenziwe futhi zalungiswa ngempumelelo yi-Cu-mediated Huisgen 1,3-dipolar cycloaddition reaction kusetshenziswa i-UAM chemistry set-up. Ngokusebenzisa izakhiwo ezihlukile ze-UAM kanye nokucubungula okuqhubekayo kokugeleza, idivayisi iyakwazi ukuvuselela ukusabela okuqhubekayo ngenkathi inikeza impendulo yesikhathi sangempela yokuqapha nokuthuthukisa ukusabela.
Ngenxa yezinzuzo zayo ezibalulekile ngaphezu komlingani wayo omkhulu, i-flow chemistry iyinsimu ebalulekile futhi ekhulayo kokubili ezindaweni zemfundo kanye nezimboni ngenxa yamandla ayo okwandisa ukukhetha kanye nokusebenza kahle kokwenziwa kwamakhemikhali. Lokhu kusabalala kusukela ekwakhiweni okulula kwama-molecule e-organic1 kuya kuma-pharmaceutical compounds2,3 kanye nemikhiqizo yemvelo4,5,6. Ngaphezu kwama-50% okusabela embonini yamakhemikhali amahle kanye nemithi kungazuza ekusebenziseni ukugeleza okuqhubekayo7.
Eminyakeni yamuva nje, kube nomkhuba okhulayo wamaqembu afuna ukufaka esikhundleni sezinto zokugqoka zeglasi noma imishini ye-flow chemistry nge-"reaction vessels" ye-customizable additive manufacturing (AM) chemistry 8. Ukwakheka okuphindaphindiwe, ukukhiqizwa okusheshayo, kanye namakhono e-3-dimensional (3D) alawa masu kuzuzisa labo abafisa ukwenza ngokwezifiso amadivayisi abo kusethi ethile yokusabela, amadivayisi, noma izimo. Kuze kube manje, lo msebenzi ugxile kakhulu ekusetshenzisweni kwamasu okuphrinta e-3D asekelwe ku-polymer njenge-sterolithography (SL)9,10,11, i-fused deposition modeling (FDM)8,12,13,14 kanye nokuphrinta kwe-inkjet 7, 15, 16. Ukuntuleka kokuqina kanye nekhono lamadivayisi anjalo lokwenza ukusabela/ukuhlaziya okubanzi kwamakhemikhali17, 18, 19, 20 kuyisici esibalulekile esivimbela ukusetshenziswa kwe-AM kabanzi kulo mkhakha17, 18, 19, 20.
Ngenxa yokusetshenziswa okwandayo kwe-flow chemistry kanye nezakhiwo ezinhle ezihambisana ne-AM, kunesidingo sokuhlola amasu athuthukile avumela abasebenzisi ukuthi bakhe imikhumbi yokusabela kokugeleza ngamakhono athuthukisiwe amakhemikhali nokuhlaziya. Lawa masu kufanele avumele abasebenzisi ukuthi bakhethe ezintweni eziqinile kakhulu noma ezisebenzayo ezikwazi ukusingatha izimo eziningi zokusabela, kuyilapho futhi kusiza izinhlobo ezahlukene zomphumela wokuhlaziya kusuka kudivayisi ukuze kuvunyelwe ukuqapha nokulawula ukusabela.
Enye inqubo yokukhiqiza eyengeziwe enekhono lokuthuthukisa ama-reactor amakhemikhali enziwe ngokwezifiso yi-Ultrasonic Additive Manufacturing (UAM). Le ndlela yokubopha ishidi eliqinile isebenzisa ukujiya kwe-ultrasonic kuma-foil ensimbi amancane ukuze iwahlanganise ndawonye ungqimba ngengqimba ngokushisa okuncane kanye nezinga eliphezulu lokugeleza kwepulasitiki 21, 22, 23. Ngokungafani nezinye ubuchwepheshe be-AM, i-UAM ingahlanganiswa ngqo nokukhiqizwa kwe-subtractive, okwaziwa ngokuthi inqubo yokukhiqiza ye-hybrid, lapho ukugaya noma ukushintshwa kwe-laser kwe-in-situ periodic computer numerical control (CNC) kuchaza ukuma kwenetha kwengqimba yezinto eziboshiwe 24, 25. Lokhu kusho ukuthi umsebenzisi akanqunyelwe yizinkinga ezihambisana nokususa izinto zokwakha ezingavuthiwe ezisele eziteshini ezincane zoketshezi, okuvame ukuba njalo ngezinhlelo ze-powder ne-liquid AM26, 27, 28. Le nkululeko yokuklama iphinde ifinyelele ekukhetheni kwezinto ezitholakalayo - i-UAM ingabopha ukuhlanganiswa kwezinto ezifanayo ngokushisa nezingafani ngesinyathelo senqubo eyodwa. Ukukhetha ukuhlanganiswa kwezinto ngale kwenqubo yokuncibilikisa kusho ukuthi izidingo zemishini nezamakhemikhali zezinhlelo ezithile zingahlangatshezwa kangcono. Ngaphezu kokubopha kwesimo esiqinile, enye Isenzakalo esihlangatshezwana naso ngesikhathi sokubophana kwe-ultrasonic ukugeleza okuphezulu kwezinto zepulasitiki emazingeni okushisa aphansi kakhulu29,30,31,32,33. Lesi sici esiyingqayizivele se-UAM singenza kube lula ukushumeka kwezinto zemishini/ezishisayo phakathi kwezingqimba zensimbi ngaphandle komonakalo. Izinzwa ezishumekiwe ze-UAM zingenza kube lula ukulethwa kolwazi lwesikhathi sangempela oluvela kudivayisi luye kumsebenzisi ngokusebenzisa ukuhlaziya okuhlanganisiwe.
Umsebenzi wababhali odlule32 ubonise ikhono lenqubo ye-UAM lokudala izakhiwo ze-microfluidic ze-3D zensimbi ezinamakhono okuzwa ahlanganisiwe.Leli yithuluzi lokuqapha kuphela.Leli phepha liveza isibonelo sokuqala se-reactor yamakhemikhali ye-microfluidic eyenziwe yi-UAM; idivayisi esebenzayo engagcini nje ngokuqapha kodwa futhi ekhuthaza ukwakheka kwamakhemikhali ngezinto zokwakha ezihlanganisiwe ngokwesakhiwo.Le divayisi ihlanganisa izinzuzo eziningana ezihambisana nobuchwepheshe be-UAM ekukhiqizweni kwamadivayisi amakhemikhali e-3D, njenge: ikhono lokuguqula imiklamo ephelele ye-3D ngqo kusuka kumamodeli wokuklama asekelwa yikhompyutha (CAD) ibe yimikhiqizo; ukwenziwa kwezinto eziningi ukuhlanganisa ukuhanjiswa okuphezulu kokushisa kanye nezinto zokwakha; kanye nokushumeka izinzwa zokushisa ngqo phakathi kwemifudlana ye-reagent ukuze kuqashwe futhi kulawulwe izinga lokushisa lokusabela ngendlela enembile. Ukukhombisa ukusebenza kwe-reactor, umtapo wezincwadi wamakhemikhali angu-1,2,3-triazole abalulekile ngokwemithi akhiwe yi-Huisgen 1,3-dipolar cycloaddition efakwe ithusi. Lo msebenzi uqokomisa indlela ukusetshenziswa kwesayensi yezinto zokwakha kanye nomklamo osizwa yikhompyutha okungavula ngayo amathuba amasha kanye namathuba ekhemistri ngocwaningo oluhlukahlukene.
Zonke izinyibilikisi kanye nama-reagents athengwe kwa-Sigma-Aldrich, Alfa Aesar, TCI noma Fischer Scientific futhi asetshenziswa ngaphandle kokuhlanzwa kwangaphambilini. Ama-spectra angu-1H kanye no-13C NMR aqoshwe ku-400 MHz kanye no-100 MHz, ngokulandelana, atholakale kusetshenziswa i-spectrometer ye-JEOL ECS-400 400 MHz noma i-spectrometer ye-Bruker Avance II 400 MHz kanye ne-CDCl3 noma (CD3)2SO njenge-solvent. Zonke izimpendulo zenziwe kusetshenziswa ipulatifomu ye-Uniqsis FlowSyn flow chemistry.
I-UAM yasetshenziswa ukwakha wonke amadivayisi kulolu cwaningo. Ubuchwepheshe basungulwa ngo-1999, futhi imininingwane yabo yobuchwepheshe, amapharamitha okusebenza kanye nentuthuko kusukela ekusungulweni kwayo kungafundwa ngezinto ezilandelayo ezishicilelwe34,35,36,37. Idivayisi (Isithombe 1) yasetshenziswa kusetshenziswa uhlelo lwe-UAM olunamandla aphezulu kakhulu, i-9kW SonicLayer 4000® UAM (Fabrisonic, OH, USA). Izinto ezikhethiwe zokwenziwa kwedivayisi yokugeleza kwakuyi-Cu-110 kanye ne-Al 6061. I-Cu-110 inokuqukethwe okuphezulu kwethusi (ubuncane bethusi obungu-99.9%), okwenza kube yinto enhle yokusabela okubangelwa yithusi, ngakho-ke isetshenziswa njenge-"ungqimba olusebenzayo ngaphakathi kwe-microreactor. I-Al 6061 O isetshenziswa njengezinto "eziningi", kanye nengqimba yokushumeka esetshenziselwa ukuhlaziya; Ukushumeka kwengxenye eyisizayo ye-alloy kanye nesimo se-annealed kuhlanganiswe nengqimba ye-Cu-110. I-Al 6061 O iyinto eboniswe ukuthi ihambisana kakhulu nezinqubo ze-UAM38, 39, 40, 41 futhi ihlolwe futhi yatholakala izinzile ngokwekhemikhali ngama-reagent asetshenziswe kulo msebenzi. Ukuhlanganiswa kwe-Al 6061 O ne-Cu-110 nakho kubhekwa njengenhlanganisela yezinto ezihambisanayo ze-UAM ngakho-ke kuyinto efanelekile yalolu cwaningo. 38,42 Lawa madivayisi abhalwe kuThebula 1 ngezansi.
Izigaba zokwenziwa kwe-reactor (1) I-substrate ye-Al 6061 (2) Ukwenziwa kwesiteshi esingezansi esisethwe ku-foil yethusi (3) Ukushumeka kwama-thermocouple phakathi kwezingqimba (4) Isiteshi esiphezulu (5) Ukungena kanye nokuphuma (6) I-reactor ye-Monolithic.
Ifilosofi yomklamo wendlela yoketshezi ukusebenzisa indlela ehlanganisiwe ukwandisa ibanga elihanjwa uketshezi ngaphakathi kwe-chip, kuyilapho kugcinwa i-chip ngobukhulu obuphathekayo. Lokhu kwanda kwebanga kuyathandeka ukwandisa isikhathi sokusebenzisana kwe-catalyst/reagent futhi kuhlinzeke ngemikhiqizo emihle kakhulu. Ama-chip asebenzisa ukugoba okungu-90° emaphethelweni endlela eqondile ukuze abangele ukuxubana okuguquguqukayo ngaphakathi kwedivayisi44 futhi andise isikhathi sokuxhumana koketshezi nomphezulu (i-catalyst). Ukuze kwandiswe ukuxubana okungatholakala, umklamo we-reactor unama-inlets amabili e-reagent ahlanganiswe ku-Y-junction ngaphambi kokungena esigabeni sokuxuba se-serpentine. I-inlet yesithathu, edlula umfudlana phakathi nendawo yokuhlala kwawo, ifakiwe ekwakhiweni kwe-multisteps reaction syntheses yesikhathi esizayo.
Zonke iziteshi zinephrofayili yesikwele (akukho ma-engeli okudweba), umphumela wokugaya kwe-CNC okwenziwa ngezikhathi ezithile okusetshenziswa ukudala i-geometry yesiteshi. Ubukhulu besiteshi bukhethwa ukuqinisekisa ukuphuma kwevolumu ephezulu (ye-microreactor), kuyilapho buncane ngokwanele ukwenza kube lula ukusebenzisana kobuso (ama-catalyst) koketshezi oluningi oluqukethwe. Usayizi ofanele usekelwe kokuhlangenwe nakho kwababhali kwangaphambilini ngamadivayisi ensimbi-uketshezi okusabela. Ubukhulu bangaphakathi besiteshi sokugcina babungu-750 µm x 750 µm kanti ivolumu yenani le-reactor yayingu-1 ml. Isixhumi esihlanganisiwe (intambo ye-1/4″—28 UNF) sifakiwe ekwakhiweni ukuvumela ukuhlangana okulula kwedivayisi nemishini ye-chemistry yokugeleza kwezentengiselwano. Usayizi wesiteshi unqunyelwe ubukhulu bezinto ze-foil, izakhiwo zayo zemishini, kanye namapharamitha okubopha asetshenziswa ngama-ultrasonic. Ngobubanzi obuthile bezinto ezithile, izinto "zizogoba" esiteshini esidaliwe. Okwamanje akukho modeli ethile yalokhu kubalwa, ngakho ububanzi besiteshi obukhulu bezinto ezithile kanye nomklamo bunqunywa ngokuhlola; kulokhu, ububanzi obungu-750 μm ngeke bubangele ukuwohloka.
Ukuma (isikwele) sesiteshi kunqunywa ngokusebenzisa umshini wokusika oyisikwele. Ukuma nosayizi weziteshi kungashintshwa yimishini ye-CNC esebenzisa amathuluzi okusika ahlukene ukuze kutholakale amazinga okugeleza ahlukene kanye nezici. Isibonelo sokudala isiteshi esinomumo ogobile kusetshenziswa ithuluzi elingu-125 μm singatholakala emsebenzini we-Monaghan45. Lapho ungqimba lwe-foil lubekwe ngendlela ehlelekile, ukumbozwa kwezinto ze-foil phezu kweziteshi kuzoba nokuphela okuyisicaba (isikwele). Kulo msebenzi, ukuze kugcinwe ukulingana kwesiteshi, kusetshenziswe uhlaka lwesikwele.
Ngesikhathi sokuma okuhleliwe kusengaphambili ekukhiqizweni, ama-probe okushisa e-thermocouple (Uhlobo K) afakwa ngqo ngaphakathi kwedivayisi phakathi kwamaqembu eziteshi eziphezulu nezingezansi (Isithombe 1 - Isigaba 3). Lawa ma-thermocouple angaqapha izinguquko zokushisa kusukela ku-−200 kuya ku-1350 °C.
Inqubo yokufaka insimbi yenziwa uphondo lwe-UAM kusetshenziswa i-foil yensimbi engu-25.4 mm ububanzi, ubukhulu obuyi-150 micron. Lezi zingqimba ze-foil zihlanganiswa ochungechungeni lwemichilo eseduze ukuze zimboze yonke indawo yokwakha; usayizi wezinto ezifakiwe mkhulu kunomkhiqizo wokugcina njengoba inqubo yokususa ikhiqiza ukuma kokugcina kwenetha. Umshini wokugaya we-CNC usetshenziselwa umshini wokulinganisa imingcele yangaphandle neyangaphakathi yemishini, okuholela ekuqedweni kobuso bemishini neziteshi ezilingana nepharamitha yenqubo yethuluzi elikhethiwe kanye ne-CNC (cishe i-1.6 μm Ra kulesi sibonelo). Umjikelezo wokufaka izinto ze-ultrasonic oqhubekayo kanye nomshini wokugaya usetshenziswa kuyo yonke inqubo yokukhiqiza idivayisi ukuqinisekisa ukuthi ukunemba kobukhulu kuyagcinwa futhi ingxenye eqediwe izohlangabezana namazinga okunemba kokugaya kokuqeda kwe-CNC. Ububanzi besiteshi esisetshenziselwa le divayisi buncane ngokwanele ukuqinisekisa ukuthi izinto ze-foil "azigobi" esiteshini soketshezi, ngakho-ke isiteshi sigcina ingxenye yesikwele. Izikhala ezingaba khona ezintweni ze-foil kanye nemingcele yenqubo ye-UAM zinqunywe ngokuhlola ngumlingani wokukhiqiza (Fabrisonic LLC, USA).
Izifundo zibonise ukuthi ukusabalala okuncane kwezinto ezibonakalayo kwenzeka ku-UAM bonding interface 46, 47 ngaphandle kokwelashwa okwengeziwe kokushisa, ngakho-ke kumadivayisi akulo msebenzi, ungqimba lwe-Cu-110 luhlala luhlukile kungqimba lwe-Al 6061 futhi lushintsha ngokuzumayo.
Faka isilawuli sokucindezela emuva esingu-250 psi (1724 kPa) esilinganiswe kusengaphambili endaweni yokuphuma kwe-reactor bese upompa amanzi nge-reactor ngesilinganiso esingu-0.1 kuya ku-1 mL min-1. Ingcindezi ye-reactor yaqashwa kusetshenziswa inzwa yokucindezela yesistimu eyakhelwe ngaphakathi ye-FlowSyn ukuqinisekisa ukuthi uhlelo lungagcina ingcindezi engaguquki. Ama-gradients okushisa angaba khona kulo lonke i-flow reactor ahlolwe ngokuhlonza noma yimuphi umehluko phakathi kwama-thermocouple afakwe ngaphakathi kwe-reactor kanye nalawo afakwe ngaphakathi kwe-FlowSyn chip heating plate. Lokhu kufezwa ngokushintsha izinga lokushisa le-hotplate elihleliwe phakathi kuka-100 no-150 °C ngama-increments angu-25 °C nokuqaphela noma yimuphi umehluko phakathi kwamazinga okushisa ahleliwe narekhodiwe. Lokhu kufezwe kusetshenziswa i-tc-08 data logger (PicoTech, Cambridge, UK) kanye nesofthiwe ye-PicoLog ehambisanayo.
Izimo zokusabela kwe-cycloaddition ze-phenylacetylene ne-iodoethane zenziwe ngcono (Iskimu 1- Iskimu 1- Iskimu 1- Iskimu senziwa ngcono nge-phenylacetylene ne-iodoethane). Lokhu kulungiswa kwenziwe ngendlela yokuklama okuphelele kwe-factorial of experiments (DOE), kusetshenziswa izinga lokushisa nesikhathi sokuhlala njengemingcele eguquguqukayo, ngenkathi kulungiswa isilinganiso se-alkyne:azide ku-1:2.
Izixazululo ezihlukene ze-sodium azide (0.25 M, 4:1 DMF:H2O), iodoethane (0.25 M, DMF), kanye ne-phenylacetylene (0.125 M, DMF) zalungiswa. I-aliquot engu-1.5 mL yesisombululo ngasinye yaxutshwa futhi yaphonswa nge-reactor ngesilinganiso sokugeleza kanye nokushisa okufunwayo. Impendulo yemodeli yathathwa njengesilinganiso sendawo ephezulu yomkhiqizo we-triazole kuya ku-phenylacetylene starting material futhi yanqunywa yi-high performance liquid chromatography (HPLC). Ukuze kuhambisane nokuhlaziywa, zonke izimpendulo zathathwa isampula ngemuva nje kokuba ingxube yempendulo ishiye i-reactor. Ububanzi bepharamitha obukhethiwe bokwenza ngcono buboniswe kuThebula 2.
Zonke izibonelo zahlaziywa kusetshenziswa uhlelo lwe-Chromaster HPLC (VWR, PA, USA) oluqukethe ipompo ye-quaternary, i-oven yekholomu, i-UV detector eguquguqukayo kanye ne-autosampler. Ikholomu yayiyi-Equivalence 5 C18 (VWR, PA, USA), usayizi ongu-4.6 × 100 mm, usayizi wezinhlayiya ezingu-5 µm, egcinwe ku-40 °C. I-solvent yayiyi-isocratic 50:50 methanol:water ngesilinganiso sokugeleza esingu-1.5 mL.min-1. Umthamo womjovo wawungu-5 µL kanti ubude bomjovo babungu-254 nm. Indawo ye-% peak yesampula ye-DOE ibalwa kusukela ezindaweni ze-peak zemikhiqizo ye-alkyne ne-triazole esele kuphela. Ukujova kwezinto zokuqala kuvumela ukuhlonza iziqongo ezifanele.
Ukuhlanganisa umphumela wokuhlaziywa kwe-reactor nesofthiwe ye-MODDE DOE (Umetrics, Malmö, Sweden) kuvumele ukuhlaziywa okujulile kwemikhuba yemiphumela kanye nokunqunywa kwezimo zokusabela ezifanele zalesi cycloaddition. Ukusebenzisa i-optimizer eyakhelwe ngaphakathi nokukhetha wonke amagama abalulekile emodeli kuveza isethi yezimo zokusabela ezenzelwe ukukhulisa indawo ephezulu yomkhiqizo ngenkathi kunciphisa indawo ephezulu yezinto zokuqala ze-acetylene.
Ukushiswa kwethusi elingaphezulu ngaphakathi kwegumbi lokusabela kwe-catalytic kufezwe kusetshenziswa isixazululo se-hydrogen peroxide (36%) esigeleza egumbini lokusabela (isilinganiso sokugeleza = 0.4 mL min-1, isikhathi sokuhlala = 2.5 min) ngaphambi kokwenziwa komtapo wolwazi ngamunye we-triazole compound.
Uma sekutholakale isethi efanele yezimo, zafakwa kuhlu lwe-acetylene kanye ne-haloalkane derivatives ukuvumela ukuhlanganiswa kokuhlanganiswa komtapo wolwazi omncane, ngaleyo ndlela kwasungulwa ikhono lokusebenzisa lezi zimo kuhlu olubanzi lwe-reagents ezingaba khona (Isithombe 1).2).
Lungisa izixazululo ezihlukene ze-sodium azide (0.25 M, 4:1 DMF:H2O), ama-haloalkanes (0.25 M, DMF) kanye nama-alkynes (0.125 M, DMF). Ama-aliquot angu-3 mL esisombululo ngasinye axutshwe futhi adonswa nge-reactor ku-75 µL.min-1 kanye no-150 °C. Ivolumu iyonke yaqoqwa yafakwa ebhodleleni futhi yaxutshwa ne-10 mL ye-ethyl acetate. Isixazululo sesampula sagezwa nge-3 × 10 mL yamanzi. Izendlalelo zamanzi zahlanganiswa futhi zakhishwa nge-10 mL ye-ethyl acetate; izendlalelo eziphilayo zabe sezihlanganiswa, zagezwa nge-3 x 10 mL ye-brine, zomiswa phezu kwe-MgSO4 futhi zahlungwa, bese i-solvent isuswa ku-vacuo. Amasampula ahlanzwa nge-column chromatography ku-silica gel kusetshenziswa i-ethyl acetate ngaphambi kokuhlaziywa ngenhlanganisela ye-HPLC, 1H NMR, 13C NMR kanye ne-high resolution mass spectrometry (HR-MS).
Zonke izinhlayiya zatholakala kusetshenziswa i-Thermofischer precision Orbitrap resolution mass spectrometer ene-ESI njengomthombo we-ionization. Wonke amasampula alungiswa kusetshenziswa i-acetonitrile njenge-solvent.
Ukuhlaziywa kwe-TLC kwenziwe kuma-silica plate asekelwe yi-aluminium. Ama-plate aboniswe ngokukhanya kwe-UV (254 nm) noma i-vanillin staining kanye nokushisa.
Zonke izibonelo zahlaziywa kusetshenziswa uhlelo lwe-VWR Chromaster (VWR International Ltd., Leighton Buzzard, UK) oluhlonyiswe nge-autosampler, i-column oven binary pump kanye ne-single wavelength detector. Ikholomu esetshenzisiwe kwakuyi-ACE Equivalence 5 C18 (150 × 4.6 mm, Advanced Chromatography Technologies Ltd., e-Aberdeen, eScotland).
Imijovo (5 µL) yenziwe ngqo ngengxube ye-crude reaction exutshwe (1:10 dilution) futhi yahlaziywa ngamanzi:methanol (50:50 noma 70:30), ngaphandle kwamanye amasampula asebenzisa uhlelo lwe-solvent lwe-70:30 (olukhonjiswe njengenombolo yenkanyezi) ngesilinganiso sokugeleza esingu-1.5 mL/min. Ikholomu igcinwe ku-40 °C. Ububanzi be-detector bungu-254 nm.
Indawo ephakeme engu-% yesampula ibalwa kusukela endaweni ephakeme ye-alkyne esele, umkhiqizo we-triazole kuphela, futhi ukufakwa kwezinto zokuqala kuvumela ukuhlonza iziqongo ezifanele.
Zonke izibonelo zahlaziywa kusetshenziswa i-Thermo iCAP 6000 ICP-OES. Zonke izindinganiso zokulinganisa zalungiswa kusetshenziswa isisombululo esijwayelekile se-1000 ppm Cu ku-2% nitric acid (SPEX Certi Prep). Zonke izindinganiso zalungiswa kusisombululo se-5% DMF kanye ne-2% HNO3, futhi zonke izibonelo zahlanjululwa ngokuphindwe ka-20 kusisombululo sesampula se-DMF-HNO3.
I-UAM isebenzisa ukushisela kwensimbi ye-ultrasonic njengendlela yokubopha izinto ze-foil yensimbi ezisetshenziselwa ukwakha umhlangano wokugcina. Ukushisela kwensimbi ye-ultrasonic kusebenzisa ithuluzi lensimbi elidlidlizayo (elibizwa ngokuthi uphondo noma uphondo lwe-ultrasonic) ukufaka ingcindezi kungqimba lwe-foil/ungqimba oluhlanganisiwe ngaphambilini ukuze luboshwe ngenkathi kudlidlizwa izinto. Ukuze kusebenze ngokuqhubekayo, i-sonotrode iyisilinda futhi igoqa phezu kobuso bezinto, ibophe yonke indawo. Lapho kusetshenziswa ingcindezi nokudlidliza, ama-oxide ebusweni bezinto angaqhekeka. Ingcindezi eqhubekayo nokudlidliza kungabangela ukungahambi kahle kwezinto ukuthi ziwe 36. Ukuxhumana okuseduze nokushisa okubangelwa endaweni kanye nengcindezi bese kuholela ekuboshweni kwesimo esiqinile ezindaweni ezibonakalayo; kungasiza futhi ukunamathela ngezinguquko zamandla obuso 48. Uhlobo lwendlela yokubopha lunqoba izinkinga eziningi ezihambisana nokushisa okuguquguqukayo okuncibilikayo kanye nemiphumela yokushisa ephezulu eshiwo kwamanye amasu okukhiqiza okungeziwe. Lokhu kuvumela ukubopha okuqondile (okungukuthi, ngaphandle kokuguqulwa kobuso, izigcwalisi noma izinamathiseli) zezingqimba eziningi zezinto ezahlukene zibe yisakhiwo esisodwa esihlanganisiwe.
Isici sesibili esihle se-UAM izinga eliphezulu lokugeleza kwepulasitiki okubonwa ezintweni zensimbi, ngisho nasemazingeni okushisa aphansi, okungukuthi ngaphansi kakhulu kwephuzu lokuncibilika kwezinto zensimbi. Ukuhlanganiswa kokuguquguquka kwe-ultrasonic kanye nokucindezela kubangela amazinga aphezulu okufuduka kwemingcele yendawo kanye nokuvuselelwa kabusha ngaphandle kokwanda okukhulu kokushisa okuhlotshaniswa ngokwesiko nezinto ezinkulu. Ngesikhathi sokwakhiwa kwenhlangano yokugcina, lesi simo singasetshenziswa ukufaka izingxenye ezisebenzayo nezingasebenzi phakathi kwezingqimba ze-foil yensimbi, ungqimba ngengqimba. Izinto ezifana nemicu ye-optical 49, ukuqinisa 46, i-electronics 50, kanye ne-thermocouples (lo msebenzi) zonke zifakwe ngempumelelo ezakhiweni ze-UAM ukudala izinhlangano ezisebenzayo nezingasebenzi.
Kulo msebenzi, kokubili amathuba okuhlanganisa izinto ezahlukene kanye nokuhlanganisa i-UAM asetshenziswe ukudala i-microreactor yokugcina izinga lokushisa e-catalytic.
Uma kuqhathaniswa ne-palladium (Pd) nezinye izinto ezivame ukusetshenziswa njenge-metal catalyst, i-Cu catalysis inezinzuzo eziningana: (i) Ngokomnotho, i-Cu ishibhile kunezinye izinsimbi eziningi ezisetshenziswa ku-catalysis ngakho-ke iyindlela ekhangayo embonini yokucubungula amakhemikhali (ii) Ububanzi bezindlela zokuhlangana ezihlanganisiwe ze-Cu-catalyzed buyanda futhi bubonakala buhambisana kancane nezindlela ezisekelwe ku-Pd51,52,53 (iii) Izindlela zokusabela ezihlanganisiwe ze-Cu zisebenza kahle uma kungekho ezinye i-ligands, Lawa ma-ligands avame ukuba lula ngokwesakhiwo futhi angabizi uma efunwa, kanti lawo asetshenziswa ku-Pd chemistry avame ukuba yinkimbinkimbi, ayabiza, futhi azwela emoyeni (iv) I-Cu, eyaziwa kakhulu ngekhono layo lokubopha ama-alkynes ekuhlanganiseni, Isibonelo, ukuhlanganiswa kwe-Sonogashira okuhlanganisiwe kwe-bimetallic kanye ne-cycloaddition ene-azides (i-click chemistry) (v) I-Cu iyakwazi futhi ukukhuthaza i-arylation yama-nucleophile amaningana ku-Ullmann-type reactions.
Izibonelo zokwahlukahluka kwazo zonke lezi zindlela zokusabela ziboniswe muva nje lapho kukhona i-Cu(0). Lokhu kungenxa kakhulu embonini yezemithi kanye nokugxila okukhulayo ekubuyiselweni nasekusetshenzisweni kabusha kwe-metal catalyst55,56.
Iqanjwe nguHuisgen ngawo-1960s57, ukusabela kwe-cycloaddition ye-1,3-dipolar phakathi kwe-acetylene ne-azide ku-1,2,3-triazole kubhekwa njengokusabela kokubonisana. Izingxenye ze-triazole eziyi-1,2,3 eziphumelelayo zithakazelisa kakhulu njenge-pharmacophore emkhakheni wokutholwa kwemithi ngenxa yezicelo zazo zebhayoloji kanye nokusetshenziswa kwazo ekwelashweni okuhlukahlukene 58.
Lokhu kusabela kwaqala ukugqama futhi lapho uSharpless nabanye bethula umqondo we-“click chemistry”59. Igama elithi “click chemistry” lisetshenziselwa ukuchaza isethi eqinile, ethembekile nekhethayo yokusabela kokuhlanganiswa okusheshayo kwamakhemikhali amasha kanye nemitapo yolwazi ehlanganisiwe nge-heteroatom linkage (CXC)60 Ukukhanga kokwenziwa kwalezi zindlela zokusabela kuvela ekuvuneni kwazo okuphezulu okuhlobene, izimo zokusabela zilula, ukumelana nomoya-mpilo namanzi, kanye nokuhlukaniswa komkhiqizo kulula61.
I-Huisgen 1,3-dipole cycloaddition yakudala ayiyona eyesigaba "se-click chemistry". Kodwa-ke, iMedal kanye neSharpless babonise ukuthi lesi sigameko sokuxhumanisa i-azide-alkyne sidlula ku-107 kuya ku-108 lapho kukhona i-Cu(I) uma kuqhathaniswa nokusheshisa kwesilinganiso esibalulekile se-1,3-dipolar cycloaddition 62,63 okungakacatalysw. Le ndlela yokusabela ethuthukisiwe ayidingi ukuvikela amaqembu noma izimo zokusabela ezinzima futhi iveza ukuguqulwa okuphelele nokukhetha okucishe kube yi-1,4-dissubstituted 1,2,3-triazoles (anti-1,2,3-triazole) esikalini sesikhathi (Isithombe 3).
Imiphumela ye-isometric ye-Huisgen cycloadditions evamile ne-copper-catalyzed. I-Huisgen cycloadditions e-Cu(I)-catalyzed iveza ama-triazoles angu-1,4-ahlulwe esikhundleni angu-1,2,3 kuphela, kuyilapho i-Huisgen cycloadditions ebangelwa ukushisa ivame ukukhiqiza ingxube ye-1,4- kanye ne-1,5-triazoles engu-1:1 yama-stereoisomers ama-azoles.
Iningi lezinqubo zihilela ukunciphisa imithombo ye-Cu(II) ezinzile, njengokunciphisa izinhlobo ze-CuSO4 noma i-Cu(II)/Cu(0) ngokuhlanganiswa nosawoti we-sodium. Uma kuqhathaniswa nezinye izimpendulo ezibangelwa yinsimbi, ukusetshenziswa kwe-Cu(I) kunezinzuzo ezinkulu zokuba kungabizi futhi kulula ukuyiphatha.
Izifundo zokubhala amalebula e-kinetic kanye ne-isotopic ezenziwe nguWorrell et al. 65 zibonise ukuthi, esimweni sama-alkynes asekugcineni, izinto ezimbili ezifanayo zethusi zihilelekile ekusebenziseni ukusabela kwe-molecule ngayinye ku-azide. Indlela ehlongozwayo iqhubeka ngendandatho yensimbi yethusi enamalungu ayisithupha eyakhiwe ngokuhlanganiswa kwe-azide ne-acetyle yethusi ene-σ-bonded nethusi ene-π-bonded njenge-ligand ezinzile yomnikelo. Ama-derivatives ethusi e-Triazolyl akhiwa ngokuncishiswa kwendandatho, kulandelwe ukubola kwe-proton ukuhlinzeka ngemikhiqizo ye-triazole nokuvala umjikelezo we-catalytic.
Nakuba izinzuzo zamadivayisi e-flow chemistry zibhalwe kahle, kube nesifiso sokuhlanganisa amathuluzi okuhlaziya kulezi zinhlelo zokuqapha inqubo esemgqeni, ngaphakathi,67. I-UAM ibonakale iyindlela efanelekile yokuklama nokukhiqiza ama-reactor okugeleza e-3D ayinkimbinkimbi kakhulu enziwe ngezinto ezisebenzayo, ezihambisa ukushisa ezinezici zokuzwa ezifakwe ngqo (Isithombe 4).
I-aluminiyam-copper flow reactor eyenziwe ngokukhiqizwa kwe-ultrasonic additive (UAM) enesakhiwo esiyinkimbinkimbi sesiteshi sangaphakathi, ama-thermocouple ahlanganisiwe kanye negumbi lokusabela elisebenzayo. Ukuze ubone ngeso lengqondo izindlela zangaphakathi zoketshezi, i-prototype esobala eyenziwe kusetshenziswa i-sterolithography nayo iyaboniswa.
Ukuqinisekisa ukuthi ama-reactor enzelwe ukusabela kwezinto eziphilayo esikhathini esizayo, izinyibilikisi kudingeka zifudunyezwe ngokuphephile ngaphezu kwephuzu lokubila; ziyahlolwa ingcindezi kanye nokushisa. Ukuhlolwa kwengcindezi kubonise ukuthi uhlelo lugcina ingcindezi eqinile futhi engaguquki ngisho noma ingcindezi yesistimu ikhuphukile (1.7 MPa). Ukuhlolwa kwe-hydrostatic kwenziwa ekushiseni kwegumbi kusetshenziswa i-H2O njengoketshezi.
Ukuxhuma i-thermocouple efakiwe (Isithombe 1) ku-logger yedatha yokushisa kubonise ukuthi i-thermocouple yayipholile ngo-6 °C (± 1 °C) kunezinga lokushisa elihleliwe ohlelweni lwe-FlowSyn. Ngokuvamile, ukwanda kwezinga lokushisa ngo-10 °C kuphumela ekuphindweni kabili kwezinga lokusabela, ngakho-ke umehluko wokushisa wamadigri ambalwa nje ungashintsha kakhulu izinga lokusabela. Lo mehluko ubangelwa ukulahlekelwa izinga lokushisa kuwo wonke umzimba we-reactor ngenxa yokusabalalisa okuphezulu kokushisa kwezinto ezisetshenziswa enkambisweni yokukhiqiza. Lokhu kushintsha kokushisa kuyahambisana futhi ngakho-ke kungabalwa ekusethweni kwemishini ukuqinisekisa ukuthi amazinga okushisa anembile ayafinyelelwa futhi alinganiswa ngesikhathi sokusabela. Ngakho-ke, leli thuluzi lokuqapha eliku-inthanethi lisiza ukulawula okuqinile kwezinga lokushisa lokusabela futhi lenze kube lula ukwenza ngcono inqubo kanye nokuthuthukiswa kwezimo ezifanele. Lezi zinzwa zingasetshenziswa futhi ukuhlonza ama-exotherms okusabela nokuvimbela ukusabela okubalekayo ezinhlelweni ezinkulu.
I-reactor eyethulwe kulo msebenzi iyisibonelo sokuqala sokusetshenziswa kobuchwepheshe be-UAM ekwakhiweni kwama-reactor amakhemikhali futhi ibhekana nemikhawulo emikhulu eminingana ehlobene nokuphrinta kwe-AM/3D kwala madivayisi, njengokuthi: (i) ukunqoba izinkinga ezibikiwe ezihlobene nokucubungula i-copper noma i-aluminium alloy (ii) ukuxazululwa kwesiteshi sangaphakathi okuthuthukisiwe uma kuqhathaniswa namasu okuhlanganisa umbhede wempuphu (PBF) njengokuncibilikisa i-laser ekhethiwe (SLM)25,69 Ukugeleza kwezinto ezingezinhle kanye nokuthungwa kwendawo okuqinile26 (iii) Ukushisa okuncishisiwe kokucubungula, okusiza ukubopha okuqondile kwezinzwa, okungenakwenzeka kubuchwepheshe bombhede wempuphu, (v) ukunqoba izakhiwo ezimbi zemishini kanye nokuzwela kwezingxenye zezingxenye ezisekelwe ku-polymer ezinhlobonhlobo zezixazululo ezivamile ze-organic17,19.
Ukusebenza kwe-reactor kuboniswe uchungechunge lwe-alkyne azide cycloaddition reactions e-copper-catalyzed ngaphansi kwezimo zokugeleza okuqhubekayo (Umfanekiso 2). I-reactor yethusi ephrintiwe nge-ultrasonic echazwe ku-Figure 4 yahlanganiswa nesistimu yokugeleza kwezentengiselwano futhi yasetshenziselwa ukuhlanganisa ama-azide omtapo wezincwadi we-1,4-dissubstituted 1,2,3-triazoles ngokusebenzisa ukusabela okulawulwa yizinga lokushisa kwe-acetylene kanye ne-alkyl group halides lapho kukhona i-sodium chloride (Umfanekiso 3). Ukusetshenziswa kwendlela yokugeleza okuqhubekayo kunciphisa ukukhathazeka kokuphepha okungavela ezinqubweni ze-batch, njengoba lokhu kusabela kukhiqiza ama-intermediate e-azide asabela kakhulu futhi ayingozi [317], [318]. Ekuqaleni, ukusabela kwalungiselelwa i-cycloaddition ye-phenylacetylene kanye ne-iodoethane (Iskimu 1 - I-Cycloaddition ye-phenylacetylene kanye ne-iodoethane) (bheka Umfanekiso 5).
(Phezulu kwesobunxele) Isimiso sokusetha esisetshenziswe ukufaka i-reactor ye-3DP ohlelweni lokugeleza (phezulu kwesokudla) esitholwe ohlelweni olulungiselelwe (ngezansi) lwe-Huisgen cycloaddition 57 scheme phakathi kwe-phenylacetylene ne-iodoethane ukuze kulungiselelwe futhi kuboniswe izinga lokuguqulwa kokusabela kwamapharamitha alungiselelwe.
Ngokulawula isikhathi sokuhlala sama-reagent engxenyeni ye-catalytic ye-reactor nokuqapha eduze izinga lokushisa lokusabela nge-probe ye-thermocouple ehlanganiswe ngqo, izimo zokusabela zingalungiswa ngokushesha nangokunembile ngesikhathi esincane kanye nokusetshenziswa kwezinto ezibonakalayo. Kwatholakala ngokushesha ukuthi ukuguqulwa okuphezulu kakhulu kutholakale lapho kusetshenziswa isikhathi sokuhlala semizuzu eyi-15 kanye nokushisa kokusabela okungu-150 °C. Kusukela ku-coefficient plot yesofthiwe ye-MODDE, kungabonakala ukuthi kokubili isikhathi sokuhlala kanye nokushisa kokusabela kubhekwa njengamagama abalulekile emodeli. Ukusebenzisa i-optimizer eyakhelwe ngaphakathi kusetshenziswa la magama akhethiwe kudala isethi yezimo zokusabela ezenzelwe ukukhulisa izindawo eziphakeme zomkhiqizo ngenkathi kunciphisa izindawo zokuqala eziphezulu zezinto ezibonakalayo. Lokhu kulungiswa kuveze ukuguqulwa okungu-53% komkhiqizo we-triazole, okuhambisana eduze nokubikezela kwemodeli okungu-54%.
Ngokusekelwe ezincwadini ezibonisa ukuthi i-copper(I) oxide (Cu2O) ingasebenza njenge-catalytic species ephumelelayo ezindaweni zethusi ze-zero-valent kulezi zindlela zokusabela, ikhono lokufaka i-oxidize ebusweni be-reactor ngaphambi kokwenza ukusabela ekugelezeni lahlolwa70,71. Ukusabela phakathi kwe-phenylacetylene ne-iodoethane kwenziwa futhi ngaphansi kwezimo ezifanele futhi isivuno saqhathaniswa. Kwabonwa ukuthi lokhu kulungiswa kwaholela ekwandeni okukhulu ekuguqulweni kwezinto zokuqala, okwabalwa ukuthi kungaphezulu kuka-99%. Kodwa-ke, ukuqapha yi-HPLC kubonise ukuthi lokhu kuguqulwa kunciphisa kakhulu isikhathi sokuphendula eside kakhulu kuze kube cishe imizuzu engama-90, lapho umsebenzi ubonakala sengathi ulingana futhi ufinyelela "esimweni esizinzile". Lokhu kuqaphela kusikisela ukuthi umthombo womsebenzi we-catalytic utholakala ku-copper oxide engaphezulu kune-substrate yethusi ye-zero-valent. Insimbi ye-Cu i-oxidize kalula ekushiseni kwegumbi ukuze yakhe i-CuO ne-Cu2O ezingezona izendlalelo ezizivikelayo. Lokhu kuqeda isidingo sokwengeza umthombo we-copper(II) osizayo wokuhlanganiswa ndawonye71.